scholarly journals Early endosome autoantigen 1 regulates IL-1β release upon caspase-1 activation independently of gasdermin D membrane permeabilization

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Alberto Baroja-Mazo ◽  
Vincent Compan ◽  
Fátima Martín-Sánchez ◽  
Ana Tapia-Abellán ◽  
Isabelle Couillin ◽  
...  
Keyword(s):  
Pore Formation ◽  
Inflammatory Cytokine ◽  
Early Endosome ◽  
Important Process ◽  
Cytokine Release ◽  
Independent Manner ◽  
Membrane Pore ◽  
Caspase 1 ◽  
Unconventional Secretion ◽  
Secretion Pathways

AbstractUnconventional protein secretion represents an important process of the inflammatory response. The release of the pro-inflammatory cytokine interleukin (IL)-1β which burst during pyroptosis as a consequence of gasdermin D plasma membrane pore formation, can also occur through other unconventional secretion pathways dependent on caspase-1 activation. However, how caspase-1 mediates cytokine release independently of gasdermin D remains poorly understood. Here we show that following caspase-1 activation by different inflammasomes, caspase-1 cleaves early endosome autoantigen 1 (EEA1) protein at Asp127/132. Caspase-1 activation also results in the release of the endosomal EEA1 protein in a gasdermin D-independent manner. EEA1 knock-down results in adecreased release of caspase-1 and IL-1β, but the pyroptotic release of other inflammasome components and lactate dehydrogenase was not affected. This study shows how caspase-1 control the release of EEA1 and IL-1β in a pyroptotic-independent manner.

scholarly journals Gasdermin D pores are dynamically regulated by local phosphoinositide circuitry

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Ana Beatriz Santa Cruz Garcia ◽  
Kevin P. Schnur ◽  
Asrar B. Malik ◽  
Gary C. H. Mo
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Pore Formation ◽  
Inflammatory Cytokine ◽  
Living Cells ◽  
Live Cell ◽  
Pore Geometry ◽  
Cytokine Release ◽  
Cell Death Program ◽  
And Control

AbstractGasdermin D forms large, ~21 nm diameter pores in the plasma membrane to drive the cell death program pyroptosis. These pores are thought to be permanently open, and the resultant osmotic imbalance is thought to be highly damaging. Yet some cells mitigate and survive pore formation, suggesting an undiscovered layer of regulation over the function of these pores. However, no methods exist to directly reveal these mechanistic details. Here, we combine optogenetic tools, live cell fluorescence biosensing, and electrophysiology to demonstrate that gasdermin pores display phosphoinositide-dependent dynamics. We quantify repeated and fast opening-closing of these pores on the tens of seconds timescale, visualize the dynamic pore geometry, and identify the signaling that controls dynamic pore activity. The identification of this circuit allows pharmacological tuning of pyroptosis and control of inflammatory cytokine release by living cells.

scholarly journals Oxytocin Modulation of Maternal Behavior and Its Association With Immunological Activity in Rats With Cesarean Delivery

ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142110147
Author(s):  
Tong Li ◽  
Shu-Wei Jia ◽  
Dan Hou ◽  
Xiaoran Wang ◽  
Dongyang Li ◽  
...  
Keyword(s):  
Cesarean Delivery ◽  
Maternal Behavior ◽  
Inflammatory Cytokine ◽  
Adrenocorticotropic Hormone ◽  
Brain Slices ◽  
Relative Weight ◽  
Resting Membrane Potential ◽  
Cytokine Release ◽  
Immunological Activity ◽  
Fos Expression

Oxytocin (OT), a neuropeptide produced in the supraoptic (SON) and paraventricular (PVN) nuclei, is not only essential for lactation and maternal behavior but also for normal immunological activity. However, mechanisms underlying OT regulation of maternal behavior and its association with immunity around parturition, particularly under mental and physical stress, remain unclear. Here, we observed effects of OT on maternal behavior in association with immunological activity in rats after cesarean delivery (CD), a model of reproductive stress. CD significantly reduced maternal interests to the pups throughout postpartum day 1-8. On postpartum day 5, CD decreased plasma OT levels and thymic index but increased vasopressin, interleukin (IL)-1β, IL-6 and IL-10 levels. CD had no significant effect on plasma adrenocorticotropic hormone and corticosterone levels. In the hypothalamus, CD decreased corticotropin-releasing hormone contents in the PVN but increased OT contents in the PVN and SON and OT release from hypothalamic implants. CD also increased c-Fos expression, particularly in the cytoplasm of OT neurons. Lastly, CD depolarized resting membrane potential and increased spike width while increasing the variability of the firing rate of OT neurons in brain slices. Thus, CD can increase hypothalamic OT contents and release but reduce pituitary release of OT into the blood, which is associated with depressive-like maternal behavior, increased inflammatory cytokine release and decreased relative weight of the thymus.

scholarly journals The Contribution of Microglia to Neuroinflammation in Parkinson’s Disease

2021 ◽  
Vol 22 (9) ◽  
pp. 4676
Author(s):  
Katja Badanjak ◽  
Sonja Fixemer ◽  
Semra Smajić ◽  
Alexander Skupin ◽  
Anne Grünewald
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Inflammatory Cytokine ◽  
Population Ageing ◽  
Future Research ◽  
Cytokine Release ◽  
Vicious Cycle ◽  
Inflammatory Processes ◽  
Great Evidence

With the world’s population ageing, the incidence of Parkinson’s disease (PD) is on the rise. In recent years, inflammatory processes have emerged as prominent contributors to the pathology of PD. There is great evidence that microglia have a significant neuroprotective role, and that impaired and over activated microglial phenotypes are present in brains of PD patients. Thereby, PD progression is potentially driven by a vicious cycle between dying neurons and microglia through the instigation of oxidative stress, mitophagy and autophagy dysfunctions, a-synuclein accumulation, and pro-inflammatory cytokine release. Hence, investigating the involvement of microglia is of great importance for future research and treatment of PD. The purpose of this review is to highlight recent findings concerning the microglia-neuronal interplay in PD with a focus on human postmortem immunohistochemistry and single-cell studies, their relation to animal and iPSC-derived models, newly emerging technologies, and the resulting potential of new anti-inflammatory therapies for PD.

scholarly journals Induction of macrophage pyroptosis-related factors by pathogenic E. coli high pathogenicity island (HPI) in Yunnan Saba pigs

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Chunlan Shan ◽  
Shushu Miao ◽  
Chaoying Liu ◽  
Bo Zhang ◽  
Weiwei Zhao ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Inflammatory Diseases ◽  
Pathogenicity Island ◽  
Cell Membrane Permeability ◽  
Inflammatory Factor ◽  
Related Factors ◽  
Membrane Pore ◽  
E Coli ◽  
Caspase 1 ◽  
High Pathogenicity

Abstract Background Pyroptosis plays a pivotal role in the pathogenesis of many inflammatory diseases. The molecular mechanism by which pyroptosis is induced in macrophages following infection with pathogenic E. coli high pathogenicity island (HPI) will be evaluated in our study. Results After infection with the HPI+/HPI− strains and LPS, decreased macrophage cell membrane permeability and integrity were demonstrated with propidium iodide (PI) staining and the lactate dehydrogenase (LDH) assay. HPI+/HPI−-infection was accompanied by upregulated expression levels of NLRP3, ASC, caspase-1, IL-1β, IL-18 and GSDMD, with significantly higher levels detected in the HPI+ group compared to those in the HPI− group (P < 0.01 or P < 0.05). HPI+ strain is more pathogenic than HPI− strain. Conclusion Our findings indicate that pathogenic E. coli HPI infection of Saba pigs causes pyroptosis of macrophages characterized by upregulated expression of pyroptosis key factors in the NLRP3/ASC/caspase-1 signaling pathway, direct cell membrane pore formation, and secretion of the inflammatory factor IL-1β and IL-18 downstream of NLRP3 and caspase-1 activation to enhance the inflammatory response.

Membrane pore formation at protein–lipid interfaces

2014 ◽  
Vol 39 (11) ◽  
pp. 510-516 ◽  
Author(s):  
Robert J.C. Gilbert ◽  
Mauro Dalla Serra ◽  
Christopher J. Froelich ◽  
Mark I. Wallace ◽  
Gregor Anderluh
Keyword(s):  
Pore Formation ◽  
Membrane Pore

scholarly journals Molecular Basis for Membrane Pore Formation by Bax Protein Carboxyl Terminus

Biochemistry ◽  
2012 ◽  
Vol 51 (46) ◽  
pp. 9406-9419 ◽  
Author(s):  
Suren A. Tatulian ◽  
Pranav Garg ◽  
Kathleen N. Nemec ◽  
Bo Chen ◽  
Annette R. Khaled
Keyword(s):  
Molecular Basis ◽  
Pore Formation ◽  
Carboxyl Terminus ◽  
Membrane Pore ◽  
Bax Protein

#117 Depression symptom scores predict altered pro-inflammatory cytokine release and glucocorticoid resistance in nondepressed individuals

2005 ◽  
Vol 19 (4) ◽  
pp. e60-e61
Author(s):  
Lara A. Regis ◽  
Christopher G. Engeland ◽  
Jos A. Bosch ◽  
John T. Cacioppo ◽  
Phillip T. Marucha
Keyword(s):  
Inflammatory Cytokine ◽  
Glucocorticoid Resistance ◽  
Depression Symptom ◽  
Cytokine Release ◽  
Symptom Scores

scholarly journals ATP Induces IL-1βSecretion inNeisseria gonorrhoeae-Infected Human Macrophages by a Mechanism Not Related to the NLRP3/ASC/Caspase-1 Axis

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Killen García ◽  
Gisselle Escobar ◽  
Pablo Mendoza ◽  
Caroll Beltran ◽  
Claudio Perez ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immune Evasion ◽  
Transcriptional Activation ◽  
Pore Formation ◽  
Human Monocyte ◽  
Positive Staining ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Caspase 1

Neisseria gonorrhoeae(Ngo) has developed multiple immune evasion mechanisms involving the innate and adaptive immune responses. Recent findings have reported that Ngo reduces the IL-1βsecretion of infected human monocyte-derived macrophages (MDM). Here, we investigate the role of adenosine triphosphate (ATP) in production and release of IL-1βin Ngo-infected MDM. We found that the exposure of Ngo-infected MDM to ATP increases IL-1βlevels about ten times compared with unexposed Ngo-infected MDM (P<0.01). However, we did not observe any changes in inflammasome transcriptional activation of speck-like protein containing a caspase recruitment domain (CARD) (ASC,P>0.05) and caspase-1 (CASP1,P>0.05). In addition, ATP was not able to modify caspase-1 activity in Ngo-infected MDM but was able to increase pyroptosis (P>0.01). Notably ATP treatment defined an increase of positive staining for IL-1βwith a distinctive intracellular pattern of distribution. Collectively, these data demonstrate that ATP induces IL-1βsecretion by a mechanism not related to the NLRP3/ASC/caspase-1 axis and likely is acting at the level of vesicle trafficking or pore formation.

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